In silico Molecular Docking simulation of Antiviral Peptide Cathelicidin LL-۳۷ with Acyclovir

Over the last few years, peptide-based therapeutics is explored and promisingly used due to peptide’s natural origin, low toxicity, and fewer side effects. Cathelicidin LL-۳۷ is an antimicrobial/antiviral peptide that has been found in mammals and demonstrates inhibitory activity toward several enveloped viruses. Herpes Simplex Virus (HSV) types ۱ and ۲ are generally double-stranded DNA viruses that can cause infections, including oral and genital blisters. HSV type ۱ reactivation or neo-formation may reach the Central Nervous System and trigger an acute inflammatory response contributing to severe Herpetic Simplex Encephalitis and Alzheimer’s Disease pathogenesis . HSV type ۲ is the cause of most genital herpes and can be sexually transmitted. Nowadays, Acyclovir is prescribed as a first-line drug and its mechanism of action is to prevent the synthesis of viral DNA by inhibiting DNA-Polymerase . Because of the poor oral bioavailability of Acyclovir as well as viral genome mutation that results in viral resistance and drug ineffectiveness , Cathelicidin LL-۳۷ is being investigated via computational methods in this research. Due to the lack of the experimental third structures, both the receptors, DNA-Polymerase, and envelope glycoprotein of HSV, are homology modeled by Phyre۲. Energy minimization by Yasara server and refinement by ModRefiner contribute to optimized structures of ۹۳.۲% in envelope glycoprotein and ۹۰.۶% in DNA-Polymerase. Molecular docking of Cathelicidin LL-۳۷ into HSV type ۲ envelope glycoprotein by HDock server results in ۱۴ more Hydrogen bonds and ۳۵ more non-ligand bonds in comparison to the same action on HSV type ۱ DNA-Polymerase into Acyclovir. Based on the binding energy score of envelope glycoprotein and its ligand, it can be an antiviral candidate against HSV type ۲ and used to develop effective drugs

کلیدواژه ها:

Molecular Docking ، Homology Modeling ، Antiviral Peptides ، Herpes Simplex Virus